Amino acid sequence analysis will be used to delineate structural domains in the protein complex of five subunits that constitute the nicotinic acetylcholine receptor. Topographical studies will be conducted to determine the membrane disposition of each structural domain. Attempts will be made to delineate the component parts of the ion channel structure of the receptor. Methods will be developed to study cation transport mediated by the nicotinic receptor on the physiological time scale (milliseconds) in vitro. Comprehensive approaches will be utilized in order to define a detailed mechanism of postsynaptic receptor-mediated membrane depolarization.